ALA-PDT对急性淋巴细胞白血病小鼠同种异基因骨髓移植后 GVHD和GVL的影响

目的探讨5-氨基乙酰丙酸-光动力疗法(5-aminolevulinic acid-mediated photodynamic therapy,ALA-PDT)在急性淋巴细胞白血病(ALL)小鼠骨髓移植后对移植物抗宿主病(GVHD)和移植物抗白血病作用(GVL)的影响。方法以ALL小鼠为模型,经致死剂量60Co照射后,对其进行同种异基因骨髓移植的同时,静脉输注经ALA-PDT处理的供受鼠混合淋巴细胞,同时设立骨髓细胞加脾细胞移植对照组及空白对照组。观察骨髓移植后受鼠的一般情况、30 d生存率、造血功能恢复情况以及肝脏等组织的病理学改变。结果ALA-PDT处理组小鼠30 d生存率明显高于其他各组,差异有统计学意义(P<0.01);其造血功能恢复情况及GVHD反应均较其他各组有所改善。结论ALA-PDT能明显减轻小鼠骨髓移植后GVHD反应,并保留一定的GVL作用。     

国产重组人白细胞介素-11治疗儿童急性非淋巴细胞白血病化疗后血小板减少症的疗效

目的 探讨重组人白细胞介素-11(rhIL-11)对儿童急性非淋巴细胞白血病(急非淋)化疗后血小板减少的防治作用.方法 将16例急非淋患儿随机分为治疗组和对照组,其中rhIL-11治疗组于化疗结束后24 h皮下注射rhIL-11[50 μg/(kg·d)],连用10～14 d;对照组不用rhIL-11,观察2组血小板减低持续时间、血小板输注量及血小板计数变化及不良反应的发生情况,并进行统计学处理.结果 rhIL-11组27例次中有16例次(占59.3%)不需输注血小板即可恢复正常,对照组21例次中仅3例次(占14.3%)不需输注血小板自行恢复,2组比较有显著性差异(P＜0.01);rhIL-11组血小板计数下降时间均显著短于对照组;rhIL-11组血小板计数恢复正常的时间也较对照组短,2组比较均有显著性差异(Pa＜0.01).不良反应以乏力、水肿为主,均可缓解.结论 rhIL-11可加速急非淋强化治疗后血小板的恢复,预防严重血小板减少症,减少血小板输注,其机制为刺激骨髓巨核细胞生长、分化和成熟.rhIL-11对急非淋强烈化疗后血小板减少有明显的预防和治疗作用,不良反应轻微,与化疗联用可减少出血并发症,使化疗顺利进行.     

急性髓细胞白血病患儿血清白细胞介素-3、白细胞介素-6及白细胞介素-8水平变化的意义

目的 探讨急性髓细胞白血病(AML)患儿血清IL-3、6、8水平变化及临床意义.方法 采用ELISA对58例初诊AML患儿(男34例,女24例;年龄3～16岁,平均10.19岁)化疗前后血清IL-3、6、8水平进行检测.30例健康儿童作为健康对照组(男 17例,女13例;年龄4～14岁,平均9.92岁).二组均于清晨7:30-8:00空腹抽取静脉血3 mL,常温下2 500 r/min离心 20 min,分离血清置-20 ℃冰箱保存待测.除治疗M3型AML采用全反式维A酸外,余病例均采用DA(柔红霉素加阿糖胞苷),HA(高三尖杉酯碱加阿糖胞苷)或IAE(依达比星加阿糖胞苷加依托泊甙)方案化疗,30～45 d复检骨髓像.应用SPSS 10.0软件进行统计学分析.结果 58例AML中44例获完全缓解(CR),14例未缓解(NR).AML初诊患儿血清IL-3水平显著低于健康对照组(P<0.01),而血清IL-6、IL-8水平均显著高于健康对照组(Pa<0.01);AML CR组患儿血清IL-3水平较初诊时显著升高(P<0.01),但仍显著低于健康对照组(P<0.01),IL-6、IL-8水平与健康对照组比较差异均无统计学意义(Pa>0.05); AML NR组与初诊组比较均无显著性差异(Pa>0.05).AML各亚型之间血清IL-3水平比较均无显著性差异(Pa>0.05); M1及M5患儿血清IL-6水平均显著高于其他亚型(Pa<0.01); M4及M5患儿血清IL-8水平均显著高于其他亚型(Pa<0.01).结论 AML患儿血清IL-3、6、8水平变化与AML亚型有关,观察血清IL-3、6、8水平的变化可作为判断AML患儿病情及疗效的辅助指标之一.     

白细胞介素-18与一氧化氮在急性淋巴细胞白血病的发生与复发中的意义

目的探讨白细胞介素(IL)-18和一氧化氮(NO)在小儿急性淋巴细胞白血病(ALL)的发生与复发中的意义。方法采用酶联免疫吸附法(ELISA)及Griess反应分别检测73例ALL肿瘤组与18例正常对照组血清IL-18和亚硝酸盐 硝酸盐浓度。结果肿瘤组血清IL-18浓度为(224.2±37.3)ng/L,对照组为(129.3±22.1)ng/L,肿瘤组亚硝酸盐 硝酸盐浓度为(161.1±32.5)μmol/L,对照组为(44.2±15.8)μmol/L,肿瘤组明显高于对照组。肿瘤组血清IL-18和亚硝酸盐 硝酸盐浓度与患儿性别、年龄、免疫分型类型无关。IL-18血清浓度与肿瘤复发有关,但与复发脏器类别无显著差异;而亚硝酸盐 硝酸盐浓度则与之无关。结论血清IL-18和亚硝酸盐 硝酸盐浓度对ALL患者的疾病评估具有重要意义。     

脐血培养上清中白细胞介素15 和干扰素-γ含量检测

目的　研究脐血单个核细胞 (CBMNC)经脂多糖 (LPS)刺激后生成白细胞介素 15 (IL 15 )和干扰素 γ(IFN γ)的能力。方法　采用ELISA法对 14例新生儿CB和 2 0例成人外周血 (APB)MNC经LPS刺激后培养 48h的上清进行测定。结果　CB及APBMNC经LPS刺激后培养 48h的上清中可检测到IL 15和IFN γ ,但CBMNC生成IL 15和IFN γ的能力明显低于APB[IL 15 ( 8.5 5± 0 .60 )ng/Lvs ( 10 .2 4± 1.66)ng/L ,IFN γ( 2 7.96± 5 .88)ng/Lvs ( 60 .5 9± 18.15 )ng/L ,P均 <0 .0 1]。 结论　CBMNC生成IL 15和IFN γ的能力低下 ,在一定程度上揭示了CB的免疫特性 ,同APB相比 ,CB免疫功能发育不成熟     

白细胞介素-11与儿童免疫性疾病的保护作用

白细胞介素－１１是一种多效性细胞因子，在不同组织中具有不同的生物学功能。利用 ＤＮＡ重组技术生产的重组人白细胞介素－１１不仅具有刺激多种造血祖细胞分化成熟、诱导肝细胞分泌急性相反应蛋白的特性，还具有极强的抑制单核巨噬细胞产生致炎性细胞介质和信号传导分子功能，可能在造血、抗炎、肿瘤支持治疗和自身免疫性损伤的保护等方面起重要作用。白细胞介素－１１作为一种免疫调节因子，研究其在免疫性疾病中的保护作用对寻找新的治疗途径具有临床应用价值。本文就白细胞介素－１１的生物学特性及其与儿童自身免疫性疾病的保护作用的关系作一综述。     

白细胞介素-8及其受体在小儿急性白血病骨髓单个核细胞中的表达和临床意义

目的：探讨白细胞介素8(IL8)及受体(IL8R)在小儿急性白血病骨髓单个核细胞中的表达和临床意义。方法：RTPCR法检测32例急性白血病骨髓单个核细胞IL8,IL8RmRNA表达。结果：急性髓系白血病(AML)组中有5例表达IL8(5/10),4例表达IL8R(4/10);急性淋巴细胞白血病(ALL)组中有13例表达IL8(13/22),9例表达IL8R(9/22)。IL8在急性髓系白血病组中的表达水平高于急性淋巴细胞白血病组,差异有显著性(P<0.05)。AML组中M4M5亚型中的表达水平高于M2M3,差异有显著性(P<0.05)。ALL组中B系列ALL表达水平高于TALL,差异有显著性(P<0.05)。化疗后患儿骨髓单个核细胞IL8,IL8R水平显著低于化疗前(P<0.05)。结论：小儿急性白血病有IL8,IL8R的表达,IL8尤其在AML组M4M5亚型及B系列ALL更明显,化疗后两者水平显著下降。     

去除T细胞骨髓移植研究进展

异基因骨髓移植中去除供髓Ｔ细胞能有效预防移植物抗宿主病。但骨髓去Ｔ细胞常伴随移植排斥及白血病复发率增加等问题，因此本文就去Ｔ细胞的方法和临床应用的现状及进展加以综述     

急性白血病患儿血清白细胞介素-15水平检测的意义

目的检测急性白血病(AL)患儿血清白细胞介素-15(IL-15)水平,了解IL-15水平与儿童AL的关系。方法确诊未治的急性淋巴细胞白血病(ALL)、急性非淋巴细胞白血病(ANLL)和非白血病组儿童各20例,分别收集血清及骨髓单个核细胞(BMMC);另收集20例正常儿童血清作对照。使用酶联免疫吸附法(ELISA)测定不同组别血清IL-15水平。结果ALL组、ANLL组、非白血病组及正常对照组血清IL-15水平分别为(34.37±2.8)ng/L,(29.61±3.2)ng/L,(117.54±3.9)ng/L,(122.23±4.2)ng/L;其中ALL组、ANLL组分别与正常对照组进行比较均有显著意义(q=3.95,4.03Pa<0.05)。ALL组、ANLL组分别与非白血病组比较均有显著意义(q=4.17,3.76Pa<0.05)。ALL组与ANLL组比较、正常对照与非白血病组比较无明显差异(Pa>0.05)。结论检测血清IL-15水平对判断白血病患儿抗肿瘤免疫状态有一定的临床意义。     

白细胞介素-11与炎症

白细胞介素-11(IL-11)是源于骨髓基质细胞的造血生长因子家族中又一新成员,具有多种生物学活性,对其造血活性研究得最多,也最广泛。其cDNA已从灵长类动物骨髓基质细胞系PU-34的条件液中被发现。如IL-11作用于从多向祖细胞到各系定向祖细胞以及幼稚血细胞的不同分化阶段,尤其是促进了巨核细胞的增殖和成熟。1997年美国FDA(食品与药品管理局)批准Genetics Institute公司生产的重组人白细胞介素-11(rhIL-11)上市,     

Graft versus graft and graft versus host reactions after HLA-identical bone marrow transplantation in a patient with severe combined immunodeficiency with transplacentally acquired lymphoid chimerism

We describe a patient with severe combined immunodeficiency and transplacental transfer of maternal T cells who received an unfractionated HLA-identical sibling bone marrow transplant without prior conditioning. He presented prior to transplantation with a dermatitis later diagnosed as mild graft versus host disease. He had a normal absolute lymphocyte count, but proliferative responses to mitogens were very low. Antigens of the noninherited maternal HLA haplotype were detected on his blood lymphocytes. After transplantation, he developed a severe reaction including fever, cutaneous erythema and hepatosplenomegaly. Lymphocytes carrying the noninherited maternal HLA haplotype disappeared from his circulation, and his unprimed mononuclear cells became spontaneously cytotoxic to maternal lymphoblasts. He subsequently developed a lymphocytosis of 69,000/mm³, diarrhea, elevated transaminases and a worsening rash, necessitating treatment with immunosuppressive agents. Full T-cell engraftment and evidence of B-cell function later ensued and spontaneously cytotoxic lymphocytes against maternal cells disappeared by 47 days post-transplantation. We postulate that the patient's constellation of signs and symptoms after transplantation represented a combination of severe graft versus graft and mild graft versus host reactions.     

Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia

EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT.     

Outcomes of matched sibling donor bone marrow transplantation in children using single‐agent calcineurin inhibitors as prophylaxis for graft versus host disease

1 Background

Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low‐dose methotrexate. However, single‐agent CNI may be sufficient prophylaxis for a defined group of patients. Single‐agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)‐matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort.

2 Procedure

We performed a single‐institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single‐agent CNI for GVHD prophylaxis between January 2002 and December 2014.

3 Results

Fifty‐two children with a median age of 6.1 years (interquartile range [IQR] 2.5–8.3) and donor age of 6 years (IQR 3–10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty‐three (82.6%) received oral prophylaxis with single‐agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2–4 acute GVHD was 25.5%, grades 3–4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194–318) post‐transplant. Two‐year overall survival was 82.7% (95% confidence interval [CI]: 69.4–90.6%) and event‐free survival was 78.9% (95% CI: 65.1–87.7%). No patient experienced graft failure.

4 Conclusions

Single‐agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA‐identical sibling BMT. Additionally, single‐agent oral tacrolimus is a reasonable alternative to cyclosporine in this population.     

Rosai-Dorfman disease following bone marrow transplantation for pre-B cell acute lymphoblastic leukemia

A child with acute pre-B cell lymphoblastic leukemia underwent haploidentical bone marrow transplantation (BMT) after first relapse. Approximately 8 months after the BMT, he developed a soft tissue mass overlying a defect in the left frontal bone. He was found to have several additional osteolytic lesions but no evidence of lymphadenopathy or organomegaly. A biopsy of the presenting lesion demonstrated a polymorphous infiltrate composed predominantly of S-100 protein and CD68 immunoreactive histiocytic cells. Together with the presence of emperipolesis, the process was interpreted as Rosai-Dorfman (R-D) disease. He received chemotherapy with vinblastine, prednisone, 6-mercaptopurine and methotrexate and has been in remission for over 4 years. Only one previous example of acute lymphoblastic leukemia in childhood has been reported with R-D disease.     

甲氧基聚乙二醇修饰对移植物抗白血病的作用

目的探讨甲氧基聚乙二醇(mPEG)修饰供者小鼠骨髓移植物单个核细胞表面抗原对移植物抗白血病作用(graft versusleukemiaeffect,GVL)的影响。方法小鼠随机分为A、B、C、D四组。A组单纯接受60Coγ照射;B、C、D组每只小鼠腹腔接种1×106L615肿瘤细胞制成白血病模型;全部照射后,C、D组分别移植mPEG未修饰和修饰的骨髓、脾细胞悬液。观察小鼠一般反应、外周血涂片L615细胞计数、组织病理及生存时间。结果A组全部死于造血衰竭;B组死于白血病;C组全部出现明显移植物抗宿主病(GVHD)表现并死亡;D组部分小鼠(4/15)长期存活,11/15死于白血病,平均生存24.2天,长于其他组(P<0.05),生存率27%,高于其他组(P<0.05),两者差异有统计学意义。结论小鼠移植mPEG修饰骨髓移植物后保留了一定GVL作用,并且减轻GVHD。     

Autologous bone marrow transplantation in children with acute lymphoblastic leukemia

We report 25 children with acute lymphoblastic leukemia (ALL) treated with purged autologous bone marrow transplantation (ABMT) at a single center. Two children with high-risk ALL were transplanted in first remission and 23 with relapsing ALL were transplanted in second (n = 21) or third (n = 2) remission. There was no procedure-related mortality. The median time to engraftment (i.e. to reach a polymorphonuclear cell count of 0.5 x 10(9)/l) was 25 days (range 16-45 days). Seven children relapsed, four within five months after ABMT: 18 of 25 children (72%) are in continuous complete remission after a median follow-up period of 50 months (range 5-71 months). The predicted long-term disease-free survival is 65% in the whole group and 61% in those transplanted after relapse. Relapse-free children returned to normal activities within three months after ABMT. The major side effects were development of cataract and gonadal insufficiency. We consider the results promising, but our data do not allow comparison with results reported from treatment with chemotherapy alone, since some of our patients were referred from other centers and represent a selected patient group. Long-term follow-up of well-defined patient populations is necessary to evaluate the effect of ABMT.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.